Differences in cardiometabolic risk profiles between Chinese and Finnish older adults with glucose impairment and central obesity.

BACKGROUND: Obesity and ethnicity play important roles in cardiovascular complications in patients with type 2 diabetes mellitus (T2DM). This study aimed to compare cardiometabolic risk profiles between Chinese and Finnish older adults of central obesity with prediabetes or T2DM. METHODS: Study subjects were 60-74 years old and originated from two population samples. The Finnish subjects came from the Kuopio Ischemic Heart Disease (KIHD) study (n = 1089), and the Chinese subjects came from the Shanghai High-risk Diabetic Screen (SHiDS) study (n = 818). The KIHD and SHiDS studies used similar questionnaires to determine participants' baseline characteristics regarding the history of medication use and diseases and lifestyle factors. All study subjects participated in glucose tolerance tests and anthropometry assessments, including waist circumference measurements. RESULTS: Among study subjects of central obesity with prediabetes (n = 298), fasting and 2-h glucose, and fasting insulin and insulin resistance were significantly higher in Chinese than in Finnish (p < 0.0001-0.016). In addition, triglyceride (TG) level was higher and the low-density lipoprotein cholesterol (LDL) and LDL to high-density lipoprotein cholesterol (HDL) ratio were lower in Chinese than in Finnish (p < 0.0001-0.003). Among subjects of central obesity with T2DM (n = 251), Chinese subjects had significantly less proportions of antihypertensive, glycaemic control medication, and statin users as well as lower level of physical activity (p < 0.0001 for all), while higher blood pressure (p = 0.002 for systolic blood pressure and p < 0.0001 for diastolic blood pressure), TG levels (p < 0.05) and HDL (p = 0.002) than the Finnish counterparts. There were no differences in ß-cell function (HOMA-ß) between Chinese and Finnish both in prediabetes and T2DM. CONCLUSIONS: Our results indicated that Chinese and Finnish older adults of central obesity with prediabetes and T2DM had similar ß-cell function. However, Chinese individuals with prediabetes are prone to insulin resistance. Meanwhile, lipid metabolism dysfunction is also different between Chinese and Finnish. Chinese older adults of central obesity with prediabetes showed higher TG, but Finnish showed higher LDL and LDL/HDL. Strategic for T2DM prevention and treatment should be ethnically specific.

Cardiorespiratory fitness and risk of dementia: a prospective population-based cohort study.

Dementia is considered to be one of the major public health problems in light of the ageing population. Little is known about directly measured cardiorespiratory fitness as measured by maximal oxygen uptake and the risk of dementia. Our aim was to examine the relationship of cardiorespiratory fitness, as indicated by maximal oxygen uptake, with subsequent incidence of dementia. This was a population-based cohort study with an average follow-up of 22 (range 0.22-29.8) years from eastern Finland. About 2,031 men with a mean age of 52.8 years of age and no history of dementia or pulmonary disease at baseline participated in the study. Among these men, 208 cases of dementia occurred. Maximal oxygen uptake (ml/kg/min) was measured during exercise testing at baseline. One standard deviation increase in VO2max was associated with a 20% decrease in dementia. Cardiorespiratory fitness was inversely related to the risk of dementia. Men with low cardiorespiratory fitness (VO2max < 23.7 ml/kg/min, lowest quintile) had a 1.92-fold (1.24-2.967, P = 0.003), risk of dementia as compared with men who had high cardiorespiratory fitness (VO2max >36.5 ml/kg/min, highest quintile) after adjusting for age and examination years. In a multivariate model, low cardiorespiratory fitness was associated with a 1.95-fold (1.24-3.05, P = 0.003) risk of dementia. Our findings show that low cardiorespiratory fitness was associated with an increased risk of dementia.

The joint impact of prediagnostic inflammatory markers and cardiorespiratory fitness on the risk of cancer mortality.

Independently, cardiorespiratory fitness (CRF), C-reactive protein (CRP), and leukocyte count have been shown to predict cancer death. Little is known about the joint impact of CRF and prediagnostic markers of inflammation, particularly leukocyte count and CRP, and their prognostic value with cancer death. The aim of this study was to explore the association between prediagnostic inflammatory markers and CRF with cancer mortality. A population-based cohort of 2270 men from Eastern Finland with no cancer history at baseline participated in the study. CRP, leukocyte count, and CRF data were among the measures collected at baseline. Blood leukocyte count was measured with a cell counter, and serum CRP concentrations were measured using an immunometric assay. The highest value or plateau of directly measured oxygen consumption by a respiratory gas analyzer during an incremental exercise test to exhaustion was used to describe CRF. Over an average follow-up of 22 years, 272 cases of cancer mortality occurred. In a multivariate model, the joint impact of high leukocyte count (>5.40 × 109 /L) and low CRF (VO2 max < 30.08 mL kg-1  min-1 ) had a 1.85-fold (95% CI 1.30-2.63, P < .01) increased risk for cancer death compared to men with low leukocyte count (<5.40 × 109 /L) and high CRF (VO2 max > 30.08 mL kg-1  min-1 ). The joint impact of CRP and CRF shared no association with cancer mortality in a multivariate model. The joint impact of high leukocyte count and low CRF increases risk for cancer death, suggesting it is a better predictor of cancer death compared to the joint impact of CRP and CRF.

Cross-country skiing is associated with lower all-cause mortality: A population-based follow-up study.

The prospective relationship between leisure-time cross-country skiing and any fatal events is uncertain. We aimed to assess the associations of leisure-time cross-country skiing habits with the risk of all-cause mortality in a general population. A 12-month physical activity questionnaire was used at baseline to assess the frequency, average duration, and intensity of cross-country skiing in a prospective population-based cohort of 2087 middle-aged men from eastern Finland. Hazard ratios (HRs; 95% confidence intervals) were calculated for all-cause mortality. During a median (interquartile range) follow-up of 26.1 (18.7-28.0) years, 1028 all-cause mortality outcomes were recorded. In analyses adjusted for several established risk factors and other potential confounders, when compared to men who did not do any cross-country skiing, the HRs (95% CIs) of all-cause mortality were 0.84 (0.73-0.97) and 0.80 (0.67-0.96) for men who did 1-200 and >200 metabolic equivalent-hours per year of cross-country skiing, respectively. Similarly, compared to men who did not do any cross-country skiing, the corresponding adjusted HRs (95% CIs) for all-cause mortality were 0.84 (0.72-0.97) and 0.82 (0.69-0.97) for men who did 1-60 min/wk and >60 min/wk of cross-country skiing, respectively. The associations were similar across several subgroups, except for evidence of effect modification by body mass index and history of diabetes. Total volume as well as duration of leisure-time cross-country skiing is each inversely and independently associated with all-cause mortality in a middle-aged Caucasian male population.

Efficient reversible phase mask for TiO2 submicron gratings directly printed on cylindrical surfaces.

In this article we present a radial phase mask specially designed and manufactured for direct micro-structuration under UV photolithography of a cylindrical surface covered by a photoresist TiO2 film. The period of the phase mask is sub-micron (between 480 nm and 720 nm) and allows direct printing on several types of cylindrical components. With this dedicated reversible phase mask we have demonstrated the feasibility of a TiO2 grating with a period of 960 nm, printed on a SiO2 cylinder or inside a SiO2 tube of 8 mm diameter.

Serum fructosamine and risk of cardiovascular and all-cause mortality: a 24-year prospective population-based study.

BACKGROUND AND AIMS: The association between fructosamine and cardiovascular complications is not well established. We sought to evaluate whether serum fructosamine may be a risk factor for cardiovascular and all-cause mortality in nondiabetic subjects. METHODS AND RESULTS: Fructosamine and other cardiovascular risk factors were measured in a sample of 1909 nondiabetic middle-aged men without a known history of coronary heart disease (CHD) at baseline. Associations between baseline fructosamine levels and fatal CHD and cardiovascular disease (CVD) events, and all-cause mortality were estimated using a Cox regression analysis, progressively adjusted for potential confounders. Mean baseline age was 52 years and 30% were smokers. During a median follow-up of 24 years (interquartile range: 18-26 years), 177 (9%) fatal CHD, 289 (15%) fatal CVD, and 728 (38%) all-cause mortality events occurred. In analyses adjusted for several conventional risk factors (i.e., age, systolic blood pressure, smoking, LDL- and HDL-cholesterol), the hazard ratios (HRs) comparing top vs bottom quartile of serum fructosamine levels resulted: 1.33 (95% CI: 0.97, 1.82; p = 0.078) for CHD death and 0.93 (0.72, 1.19; p = 0.567) for CVD death, and 1.04 (0.89, 1.22; p = 0.617) for all-cause mortality. In similar comparisons, further adjustments for body mass index, alcohol consumption, C-reactive protein, and fasting plasma glucose did not materially change these estimates. The exclusion of participants with prevalent CVD at baseline yielded similar results. CONCLUSION: In our cohort of nondiabetic men without known CHD, baseline fructosamine levels were not independently associated with cardiovascular and all-cause mortality. Further studies are warranted to confirm these results in other populations.

Association between direct measurement of active serum calcium and risk of type 2 diabetes mellitus: A prospective study.

BACKGROUND AND AIMS: Previous prospective studies showing a positive association between serum calcium and incidence of type 2 diabetes mellitus (T2DM) have relied on total calcium or an indirect estimate of active, ionized calcium (iCa). We aimed to assess this relationship using a direct measurement of iCa. METHODS AND RESULTS: iCa and cardiometabolic risk factors were measured in a population-based sample of 2350 men without a known history of T2DM at baseline. Associations between iCa levels and incident cases of T2DM (self-reported, ascertained with a glucose tolerance test, or determined by record linkage to national registers) were estimated using Cox regression analyses adjusted for potential confounders. At baseline, mean (standard deviation) age was 53 (5) years and mean iCa 1.18 (0.05) mmol/L. During a median follow-up of 23.1 years, 140 new cases of T2DM were recorded. In a multivariable analysis adjusted for age, body mass index, systolic blood pressure, serum HDL-cholesterol, and family history of T2DM, there was no association comparing second (hazard ratio 0.84; 95% confidence interval 0.59-1.18), third (0.77; 0.52-1.14), or fourth (0.98; 0.69-1.39) vs first quartile of iCa (p for trend 0.538); further adjustment for C-reactive protein, physical activity level, and triglycerides did not change the estimates (p for trend 0.389). CONCLUSION: In this study, we did not find evidence of an association between direct measurement of active calcium and risk of T2DM. Further studies are needed to confirm our findings and define the relationship between factors influencing indirect calcium estimation and incident T2DM.

The frequency of alcohol consumption is associated with the stroke mortality.

OBJECTIVES: The purpose of this study was to examine the association between the frequency of alcohol consumption and stroke mortality among eastern Finnish men. MATERIAL AND METHODS: This study is a population-based sample of men with an average follow-up of 20.2 years. A total of 2609 men with no history of stroke at baseline participated in the study. During the follow-up, 66 deaths from stroke occurred. RESULTS: After adjustment for systolic blood pressure, smoking, BMI, diabetes, and socioeconomic status, the relative risk (RR) among men who consumed alcohol <0.5 times per week was 0.70 (95% CI, 0.30-1.66; P = 0.419) compared with nondrinkers. Respective RR was 1.08 (95% CI, 0.51-2.27; P = 0.846) for men with alcohol consumption of 0.5-2.5 times per week and 2.44 (95% CI, 1.11-5.40; P = 0.027) for men who consumed alcohol >2.5 times per week after adjustment for risk factors. When the total amount of alcohol consumption (g/week) was taken into account with other covariates, RR was 0.71 (95% CI, 0.30-1.68; P = 0.437) for men with alcohol consumption <0.5 times per week and 1.16 (95% CI, 0.54-2.50; P = 0.704) among men who consumed alcohol 0.5-2.5 times per week. Among men who consumed alcohol >2.5 times per week compared with nondrinkers, RR was 3.03 (95% CI, 1.19-7.72; P = 0.020). CONCLUSIONS: This study shows a strong association between the frequency of alcohol consumption and stroke mortality, independent of total amount of alcohol consumption. The risk of stroke death was the highest among men who consumed alcohol >2.5 times per week.

Hangover and the risk of stroke in middle-aged men.

OBJECTIVES: The aim of this study was to examine the association between hangover and the risk of stroke. MATERIAL AND METHODS: A population-based sample of men with an average follow-up of 15.7 years. 2466 men with no history of stroke at baseline participated. Two hundred and six strokes occurred, of which 167 were ischemic strokes. RESULTS: The age-adjusted, relative risk (RR) for any stroke among men with ≥1 hangover per year was 2.33-fold (95% confidence interval (CI), 1.19-4.56; P = 0.013) relative to men without hangover, and 2.99-fold (95% CI, 1.52-5.86; P = 0.001) for ischemic stroke, respectively. After adjustment for age, smoking, high density lipoprotein (HDL)-cholesterol, LDL-cholesterol, BMI, SBP, myocardial ischemia during exercise, symptomatic coronary heart disease (CHD) and CHD in family, C-reactive protein, diabetes, and total alcohol consumption, the RR for any stroke was 1.94-fold (95% CI, 0.95-3.96; P = 0.070) and 2.58-fold (95% CI, 1.24-5.36; P = 0.011) for ischemic stroke among men with hangovers. Additional adjustment of atrial fibrillation and cardiac failure and risk was 2.45-fold (95% CI, 1.18-5.12; P = 0.017) for ischemic strokes. CONCLUSION: This study shows that at least one hangover a year is related to an increased risk of ischemic stroke in men.

The Interplay between Systolic Blood Pressure, Sauna Bathing, and Cardiovascular Mortality in Middle-Aged and Older Finnish Men: A Cohort Study.

OBJECTIVES: Elevated systolic blood pressure (SBP) is associated with an increased risk of cardiovascular disease (CVD) mortality, whereas frequent sauna bathing reduces the risk. Whether frequent sauna bathing mitigates CVD mortality among adults with elevated SBP has not been previously investigated. DESIGN AND SETTING: We examined the interactions between SBP and frequency of sauna bathing (FSB) with the risk of CVD mortality in a cohort of Caucasian men. PARTICIPANTS: The Kuopio Ischaemic Heart Disease Study cohort comprising of 2,575 men aged 42-61 years at baseline was employed for this prospective study analysis. MEASUREMENTS: Resting blood pressure was measured using a standardized protocol and sauna bathing habits were assessed by a self-administered questionnaire. Systolic blood pressure was categorized as normal and high (<140 and ≥140 mmHg, respectively) and FSB as low and high (defined as ≤ 2 and 3-7 sessions/week, respectively). RESULTS: A total of 744 CVD deaths were recorded during a median follow-up of 27.8 yr. Comparing high vs normal SBP, the multivariable-adjusted HR (95% CI) for CVD mortality was 1.44 (1.23-1.68). Comparing low vs high FSB, the multivariable-adjusted HR (95% CI) for CVD mortality was 1.24 (1.03-1.51). The associations persisted following mutual adjustment for each exposure. Compared with men with normal SBP-high FSB, high SBP-low FSB was associated with an increased risk of CVD mortality 1.81 (1.39-2.36), with attenuated but persisting evidence of an association for men with high SBP and high FSB 1.52 (1.06-2.16). When SBP was categorized as normal and high (<130 and ≥130 mmHg, respectively), there was no evidence of an association for men with high SBP and high FSB 1.11 (0.77-1.61). CONCLUSION: There might be an interaction between SBP, sauna bathing and CVD mortality risk in middle-aged and older Caucasian males. Frequent sauna baths may offset the increased risk of CVD mortality in men with high-normal SBP but not elevated SBP.

Subwavelength cylindrical grating by holistic phase-mask coordinate transform.

A periodic grating with an integer number of periods is fabricated at the resist-coated wall of a cylinder by exposing a circularly symmetrical planar high index phase mask to a cylindrical wave. This extends the spatial coherence features easily achievable in a planar 2D space to the 3D space of cylindrical waves and elements.

Low ß-carotene concentrations increase the risk of cardiovascular disease mortality among Finnish men with risk factors.

BACKGROUND & AIMS: Healthy diet rich in fruits and vegetables is an important factor in prevention of cardiovascular diseases (CVD). Some previous epidemiological studies have suggested that dietary and serum carotenoids are associated with decreased CVD mortality, but the results have been inconsistent. We assessed relations between the concentrations of serum carotenoids and CVD mortality among Eastern Finnish men. METHODS & RESULTS: The study population consisted of 1031 Eastern Finnish men aged 46-65 years in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) cohort. Subjects were classified quartiles according to concentrations of carotenoids and subgroups according to risk factors. Hazard ratios of serum lycopene, α-carotene and ß-carotene were estimated by the Cox proportional hazard model after adjusting for potential confounding factors. During the median 15.9-year follow-up, 122 deaths from CVDs, were identified among the cohort subjects. Low serum concentrations of ß-carotene were strongly related to an increased CVD mortality risk after adjustment for confounders. For ß-carotene, the hazard ratio (95% confidence interval) for the lowest versus highest quartile was 2.23 (1.26-3.93; P=0.006). However, the strongest risk of CVD mortality was observed among smokers with lowest levels of ß-carotene (HR=3.15, 95%, CI: 1.19-8.33; P=0.020). Other carotenoids and the sum of carotenoids were not significantly related to increased risk of CVD mortality. CONCLUSIONS: Low concentrations of serum ß-carotene concentrations may increase the risk for CVD mortality among Eastern Finnish men; thus elevated serum concentrations of ß-carotene may have clinical and public health relevance.

Plasma carotenoids are related to intima--media thickness of the carotid artery wall in men from eastern Finland.

BACKGROUND: Several previous epidemiological studies have suggested that high plasma concentrations of carotenoids may slow the development of early atherosclerosis, but results have been inconclusive. METHODS: We examined the effect of carotenoids on early atherosclerosis in a population-based study. The association between plasma carotenoid concentrations and intima-media thickness of the common carotid artery (CCA-IMT) was investigated in 1212 elderly men (aged 61-80 years) in Eastern Finland. They were examined by B-mode ultrasound to detect early signs of carotid atherosclerosis, and plasma concentrations of carotenoids were measured by high-performance liquid chromatography. RESULTS: Men in the lowest quartile of CCA-IMT had significantly higher concentrations of plasma ß-cryptoxanthin, lycopene and α-carotene than men in the highest quartile (P for the differences: 0.043, 0.045 and 0.046, respectively), after adjustment for age, examination year, body mass index, smoking, alcohol intake, years of education, symptomatic coronary heart disease (CHD) or CHD history, diabetes, low-density lipoprotein cholesterol, medications and season. The concentrations of plasma ß-cryptoxanthin, lycopene and α-carotene decreased linearly with increasing CCA-IMT. CONCLUSIONS: The results of this study suggest that high plasma concentrations of ß-cryptoxanthin, lycopene and α-carotene may be associated with decreased carotid atherosclerosis in elderly men from eastern Finland.

Two-minute heart rate recovery after cycle ergometer exercise and all-cause mortality in middle-aged men.

BACKGROUND: A slow heart rate recovery (HRR) after an exercise test is associated with an increased risk of all-cause mortality in asymptomatic individuals, but the data regarding additional prognostic information provided by HRR beyond other exercise test variables are inconsistent. We investigated the prognostic significance of HRR for premature death, particularly in relation to other exercise test variables. METHODS: The study subjects were a representative population-based sample of 1102 men (42-61 years of age) without cardiovascular disease, cancer or diabetes. HRR was defined as the difference between maximal HR and HR 2 min after a maximal symptom-limited exercise test using a cycle ergometer. The association between HRR and premature mortality was examined with Cox regression models. RESULTS: During an average follow-up of 18 years, 238 deaths occurred. HRR was an independent predictor of death [for a decrease of 12 beats min(-1) , relative risk (RR) 1.16, 95% CI 1.02-1.33, P = 0.02] after adjustment for age and established risk factors. When added in a Cox model with chronotropic response (decrease of 12 beats min(-1) , RR 1.09, 95% CI 0.93-1.27, P = 0.26) or cardiorespiratory fitness (decrease of 12 beats min(-1) , RR 1.12, 95% CI 0.98-1.30, P = 0.08), the association between a slow HRR and an increased risk of death was clearly weaker. CONCLUSION: A slow 2-min HRR after a cycle ergometer exercise test was an independent predictor of death in healthy middle-aged men after accounting for demographic and clinical characteristics. However, it was no longer predictive after accounting for chronotropic response and exercise capacity.

Glycemic index, glycemic load, and the risk of acute myocardial infarction in Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study.

BACKGROUND AND AIM: The role of dietary glycemic index (GI) and glycemic load (GL) in coronary heart disease (CHD) is unclear. Our aim was to study the association between the dietary GI and GL and the risk of acute myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 1981 Finnish men from the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study, aged 42-60 years and free of CHD at baseline. During an average follow-up time of 16.1 years, 376 new AMI events occurred. In multivariable-adjusted Cox proportional hazards models, the relative risk (RR) for AMI in the highest quartile of GI was 1.25 (95% CI: 0.92-1.69; P for trend=0.08) and for GL 1.11 (95% CI: 0.79-1.57; P for trend=0.21) when compared with the lowest quartile. For overweight (BMI ≥ 27.5 kg/m²) men, the multivariable-adjusted RR for AMI in the highest compared to the lowest tertile of GI and GL were 1.58 (95% CI: 1.03-2.43; P for trend=0.04, P for interaction=0.01) and 2.05 (95% CI: 1.30-3.23; P for trend=0.002, P for interaction=0.002), respectively. For physically less active men; energy expenditure for leisure-time physical activity < 50 kcal/d, the RR for AMI was 1.72 (95% CI: 1.07-2.76; P for trend=0.04, P for interaction 0.80) with higher GL. CONCLUSIONS: Our results suggest that both high dietary GI and GL are associated with increased risk of AMI among overweight and GL possibly among less physically active men.

Intensity of leisure-time physical activity and cancer mortality in men.

OBJECTIVE: there is a lack of evidence to show the role of exercise intensity in the prevention of cancer mortality because no previous studies have shown this relation. The relationship of leisure-time physical activity with cancer mortality was therefore assessed. METHODS: participants were from a population-based sample of 2560 men from eastern Finland with no history of cancer at baseline. Physical activity was assessed using the 12-month leisure-time physical activity questionnaire. During an average follow-up of 16.7 years, a total of 181 cancer related deaths occurred. RESULTS: an increase of 1.2 metabolic units (MET or metabolic equivalents of oxygen consumption; 1 SD in metabolic equivalents) in the mean intensity of leisure-time physical activity was related to a decrease (relative risk (RR) 0.85, 95% CI 0.72 to 0.99) in cancer mortality mainly due to lung and gastrointestinal cancers, after adjustment for age, examination year, alcohol consumption, smoking, body mass index and energy, fibre and fat intake. Men with leisure-time physical activity of more than 5.2 MET (highest quartile) had a lower (RR 0.63, 95% CI 0.40 to 0.99) cancer mortality compared with men whose mean intensity of physical activity was less than 3.7 MET (lowest quartile). The mean intensity of physical activity was related to the risk of cancer death among men who exercised at least 30 minutes per day on average. CONCLUSIONS: this prospective study indicates that the mean intensity of leisure-time physical activity is inversely associated with the risk of premature death from cancer in men.

Exercise workload, cardiovascular risk factor evaluation and the risk of stroke in middle-aged men.

OBJECTIVE: We investigated the prognostic significance of risk scores and exercise workload with respect to stroke. Background. There are no data on exercise workload combined with European Systematic Coronary Risk Evaluation (SCORE) in the prediction of stroke. METHODS: Exercise workload was measured by exercise test with an electrically braked cycle ergometer performed at baseline. The study is based on a random population-based sample of 1639 men (42-60 years) without history of type 2 diabetes or atherosclerotic cardiovascular disease including coronary heart disease, stroke or claudication. RESULTS: During an average follow-up of 16 years, a total of 97 strokes occurred, of which 71 were ischaemic strokes. Independent predictors for all strokes were European SCORE [for 1% increment, relative risk (RR): 1.12, 95% CI: 1.02 to 1.22, P=0.017), maximal workload (for 20 W increment, RR: 0.87, 95% CI: 0.80 to 0.95, P=0.003) and body mass index (for 5 kg m(-2) increment, RR: 1.08, 95% CI: 1.03 to 1.14, P=0.004), when adjusted for serum HDL, alcohol consumption, C-reactive protein, family history of coronary heart disease, exercise-induced ST changes and the use of medications for hypertension, dyslipidaemia or aspirin. The risk was 2.54-fold (95% CI: 1.27-5.09, P=0.008) for any strokes and 4.43-fold (95% CI 1.69-11.78, P=0.003) for ischaemic strokes amongst men with exercise capacity less than 162 W when compared with those with high exercise capacity over 230 W, after adjustment for risk factors. CONCLUSIONS: Low exercise workload predicts an especially high risk for stroke in the presence of high risk SCORE.

Plasma levels of haemostatic factors in patients with pulmonary embolism on admission and seven months later.

INTRODUCTION: With the exception of D-dimer, not much is known about the plasma levels of haemostatic factors during acute venous thromboembolism (VTE) compared to their basic levels in a stable phase. The goal of this study was to examine how plasma levels of factor V, VIII, XIIIa, von Willebrand factor antigen (vWF:Ag), fibrinogen, thrombomodulin evolve from the point of diagnosis of acute VTE to the end of standard treatment period. METHODS: Sixty-three consecutive patients (mean 57, range 18-86 years, 33 females) with acute pulmonary embolism (PE) were included. Laboratory samples were collected upon arrival (acute phase) and seven months later (stable phase). Fifteen similar aged individuals served as controls. RESULTS: Plasma levels of factor XIIIa (87.5% vs 117.7%, P < .001) and soluble thrombomodulin (36.6 vs 47.5 ng/L, P < .001) were lower, whereas plasma levels of vWF:Ag (2.66 vs 2.01 IU/mL, P < .001) and fibrinogen (4.3 vs 3.9 g/L, P < .05) were higher on admission compared to the stable phase. In the stable phase, vWF:Ag (2.01 vs 1.43 IU/mL, P < .01) and soluble thrombomodulin (47.5 vs 38.0 ng/mL, P < .05), but not FXIIIa levels, were higher in PE patients compared to healthy controls. CONCLUSION: This study confirms the concept of FXIIIa consumption during acute phase of VTE by showing its intraindividual normalization during the follow-up. vWF:Ag, known to be associated with the risk of VTE, was constantly elevated in the majority of the patients. Soluble thrombomodulin levels were lower in acute phase compared to stable phase, a finding which significance needs to be evaluated in the future.

Adenovirus-mediated gene transfer of a secreted form of human macrophage scavenger receptor inhibits modified low-density lipoprotein degradation and foam-cell formation in macrophages.

BACKGROUND: Macrophage scavenger receptors (MSRs) play an important role in the pathogenesis of atherosclerosis. Therefore, local modulation of MSR activity could have a beneficial effect on atherogenesis. METHODS AND RESULTS: We cloned a secreted "decoy" MSR (sMSR) that contains an extracellular portion of the human MSR type AI and constructed an adenoviral vector that directs high-level expression of sMSR in macrophages under the control of the human CD68 promoter. Expression of the sMSR protein inhibited the degradation of (125)I-labeled acetylated LDL and oxidized LDL by murine macrophages up to 90%. sMSRs also reduced acetylated LDL degradation in MSR knockout mouse peritoneal macrophages by 60% to 80%, which suggests that the decoy construct can compete for the uptake mediated via other related scavenger receptors. In addition, sMSRs inhibited foam-cell formation in murine macrophages in the presence of cytochalasin D. The mechanism of inhibition is through ligand binding to the sMSRs, which prevents the ligand binding to MSRs on cell membranes. CONCLUSIONS: The demonstration that recombinant adenovirus-mediated gene transfer of decoy sMSRs can block foam-cell formation suggests a possible new strategy for gene therapy of atherosclerosis and for the treatment of lipid accumulation after arterial manipulations.

Intravascular adenovirus-mediated VEGF-C gene transfer reduces neointima formation in balloon-denuded rabbit aorta.

BACKGROUND: Gene transfer to the vessel wall may provide new possibilities for the treatment of vascular disorders, such as postangioplasty restenosis. In this study, we analyzed the effects of adenovirus-mediated vascular endothelial growth factor (VEGF)-C gene transfer on neointima formation after endothelial denudation in rabbits. For comparison, a second group was treated with VEGF-A adenovirus and a third group with lacZ adenovirus. Clinical-grade adenoviruses were used for the study. METHODS AND RESULTS: Aortas of cholesterol-fed New Zealand White rabbits were balloon-denuded, and gene transfer was performed 3 days later. Animals were euthanized 2 and 4 weeks after the gene transfer, and intima/media ratio (I/M), histology, and cell proliferation were analyzed. Two weeks after the gene transfer, I/M in the lacZ-transfected control group was 0. 57+/-0.04. VEGF-C gene transfer reduced I/M to 0.38+/-0.02 (P:<0.05 versus lacZ group). I/M in VEGF-A-treated animals was 0.49+/-0.17 (P:=NS). The tendency that both VEGF groups had smaller I/M persisted at the 4-week time point, when the lacZ group had an I/M of 0.73+/-0.16, the VEGF-C group 0.44+/-0.14, and the VEGF-A group 0. 63+/-0.21 (P:=NS). Expression of VEGF receptors 1, 2, and 3 was detected in the vessel wall by immunocytochemistry and in situ hybridization. As an additional control, the effect of adenovirus on cell proliferation was analyzed by performing gene transfer to intact aorta without endothelial denudation. No differences were seen in smooth muscle cell proliferation or I/M between lacZ adenovirus and 0.9% saline-treated animals. CONCLUSIONS: Adenovirus-mediated VEGF-C gene transfer may be useful for the treatment of postangioplasty restenosis and vessel wall thickening after vascular manipulations.